JPH04128241A - Calba type calcitonins aqueous solution composition - Google Patents
Calba type calcitonins aqueous solution compositionInfo
- Publication number
- JPH04128241A JPH04128241A JP2243807A JP24380790A JPH04128241A JP H04128241 A JPH04128241 A JP H04128241A JP 2243807 A JP2243807 A JP 2243807A JP 24380790 A JP24380790 A JP 24380790A JP H04128241 A JPH04128241 A JP H04128241A
- Authority
- JP
- Japan
- Prior art keywords
- type
- calcitonin
- aqueous solution
- calcitonins
- carba
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 29
- 239000007864 aqueous solution Substances 0.000 title claims abstract description 28
- 108010010803 Gelatin Proteins 0.000 claims abstract description 15
- 239000008273 gelatin Substances 0.000 claims abstract description 15
- 229920000159 gelatin Polymers 0.000 claims abstract description 15
- 235000019322 gelatine Nutrition 0.000 claims abstract description 15
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 4
- 210000002966 serum Anatomy 0.000 claims abstract description 4
- 229920001184 polypeptide Polymers 0.000 claims abstract 3
- 102000055006 Calcitonin Human genes 0.000 claims description 20
- 108060001064 Calcitonin Proteins 0.000 claims description 20
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 16
- 101000741447 Gallus gallus Calcitonin Proteins 0.000 claims description 11
- VSHJAJRPRRNBEK-LMVCGNDWSA-N eel calcitonin Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CS)[C@@H](C)O)C(C)C)CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C1=CN=CN1 VSHJAJRPRRNBEK-LMVCGNDWSA-N 0.000 claims description 11
- 229960004015 calcitonin Drugs 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 6
- KSIYPKPZIBBUFR-LJNLPFSOSA-N CSCC[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(N)=O Chemical compound CSCC[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(N)=O KSIYPKPZIBBUFR-LJNLPFSOSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 claims description 5
- 108010068072 salmon calcitonin Proteins 0.000 claims description 5
- 101000741445 Homo sapiens Calcitonin Proteins 0.000 claims description 4
- 229940045644 human calcitonin Drugs 0.000 claims description 4
- YOFPFYYTUIARDI-LURJTMIESA-N (2s)-2-aminooctanedioic acid Chemical compound OC(=O)[C@@H](N)CCCCCC(O)=O YOFPFYYTUIARDI-LURJTMIESA-N 0.000 claims description 3
- 239000006172 buffering agent Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 6
- 230000006866 deterioration Effects 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 230000007062 hydrolysis Effects 0.000 abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 239000001509 sodium citrate Substances 0.000 abstract description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 abstract description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 abstract description 2
- 239000006174 pH buffer Substances 0.000 abstract description 2
- 239000001632 sodium acetate Substances 0.000 abstract description 2
- 235000017281 sodium acetate Nutrition 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
- 239000011575 calcium Substances 0.000 abstract 1
- 229910052791 calcium Inorganic materials 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- -1 polyglycerin Polymers 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000003708 ampul Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- 229920001214 Polysorbate 60 Polymers 0.000 description 4
- 239000004359 castor oil Substances 0.000 description 4
- 235000019438 castor oil Nutrition 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000047703 Nonion Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- GSGDTSDELPUTKU-UHFFFAOYSA-N nonoxybenzene Chemical compound CCCCCCCCCOC1=CC=CC=C1 GSGDTSDELPUTKU-UHFFFAOYSA-N 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 101000910302 Sus scrofa Calcitonin Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- DDPFHDCZUJFNAT-PZPWKVFESA-N chembl2104402 Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CCCCCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 DDPFHDCZUJFNAT-PZPWKVFESA-N 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- MPVXINJRXRIDDB-VCDGYCQFSA-N dodecanoic acid;(2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCCCCCC(O)=O MPVXINJRXRIDDB-VCDGYCQFSA-N 0.000 description 2
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- 238000004128 high performance liquid chromatography Methods 0.000 description 2
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- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
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- MSJMDZAOKORVFC-UAIGNFCESA-L disodium maleate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C/C([O-])=O MSJMDZAOKORVFC-UAIGNFCESA-L 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- ZPIRTVJRHUMMOI-UHFFFAOYSA-N octoxybenzene Chemical compound CCCCCCCCOC1=CC=CC=C1 ZPIRTVJRHUMMOI-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000005361 soda-lime glass Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 229910052815 sulfur oxide Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
[発明の目的]
(産業上の利用分野)
本発明はカルバ型カルシトニンを有効成分として含有す
る水溶液組成物に関する。DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Industrial Application Field) The present invention relates to an aqueous solution composition containing carba-type calcitonin as an active ingredient.
(従来の技術)
カルシトニン類は血清カルシウム低下作用を有するペプ
チド類であって、骨粗しよう症、高カルシウム血症、骨
ベージェット病等に対する治療薬として用いられている
。カルシトニン類には天然型カルシトニン及びその誘導
体が知られており、天然型の例としては、ウナギカルシ
トニン、サケカルシトニン、ブタカルシトニン、ヒトカ
ルシトエン。ニワトリカルシトニン等がある。(Prior Art) Calcitonins are peptides that have a serum calcium-lowering effect and are used as therapeutic agents for osteoporosis, hypercalcemia, Beget's disease of bone, and the like. Natural calcitonin and its derivatives are known as calcitonins, and examples of natural types include eel calcitonin, salmon calcitonin, pig calcitonin, and human calcitoene. Chicken calcitonin, etc.
カルバ型カルシトニンはこれら天然型カルシトニンの1
.7位のS−8結合をアミノスベリン酸にてC−C結合
に変えたカルシトニン誘導体であり、S−8結合をC−
C結合に変えたことによってより水溶液中の安定性が高
められる。その例としては、カルバ型ウナギカルシトニ
ン([ASU17]ウナギカルシトニン、WHO−船名
:エルカトニン)、カルバ型ニワトリカルシトニン([
ASU”]ニワトリカルシトニン)、カルバ型サケカル
シトニン([ASU17]サケカルシトニン)、カルバ
型ヒトカルシトニン([ASU17]ヒトカルシトニン
)、カルバ型ブタカルシトニン([ASU” ”Jブタ
カルシトニン)等がある。Carba-type calcitonin is one of these natural calcitonins.
.. It is a calcitonin derivative in which the S-8 bond at position 7 is changed to a C-C bond with aminosuberic acid, and the S-8 bond is changed to a C-C bond.
By changing to a C bond, stability in an aqueous solution is improved. Examples include carba-type eel calcitonin ([ASU17] eel calcitonin, WHO ship name: elcatonin), carba-type chicken calcitonin ([
These include carba-type salmon calcitonin ([ASU17] salmon calcitonin), carba-type human calcitonin ([ASU17] human calcitonin), carba-type porcine calcitonin ([ASU''J pig calcitonin), and the like.
(発明が解決しようとする課題)
カルバ型カルシトニンは前記したように優れた安定性を
有しているが、本来ペプチドであるために、加水分解に
よる劣化や振盪による変性等の劣化を避けることができ
ない。従って、水溶液製剤とし、た場合、輸送等におけ
る激しい振盪により活性が低下することがある。(Problems to be Solved by the Invention) Carba-type calcitonin has excellent stability as described above, but since it is originally a peptide, it is difficult to avoid deterioration such as deterioration due to hydrolysis or denaturation due to shaking. Can not. Therefore, when formulated as an aqueous solution, the activity may decrease due to vigorous shaking during transportation.
本発明は上記問題点に対撚してなされたもので、カルバ
型カルシトニンの水溶液製剤において、輸送中の苛酷条
件下でその安定性を保持することができるようにするこ
とを目的とするものである。The present invention has been made to address the above-mentioned problems, and the object of the present invention is to enable an aqueous solution preparation of carba-type calcitonin to maintain its stability under harsh conditions during transportation. be.
[発明の構成]
(課題を解決するための手段)
本発明者らは上記目的を達成すべく種々検討した結果、
カルバ型カルシトニン類を有効成分として含有する水溶
液組成物において、ゼラチンを0.01〜20%W/V
含有し、pHを5〜7に調整することによって、カルバ
型カルシトニン類の加水分解を抑制し、かつ振盪による
劣化を防止することができることを見出した。[Structure of the invention] (Means for solving the problem) As a result of various studies to achieve the above object, the present inventors have found that
In an aqueous solution composition containing carba-type calcitonins as an active ingredient, gelatin is added at 0.01 to 20% W/V.
It has been found that by adjusting the pH to 5 to 7, hydrolysis of carba-type calcitonins can be suppressed and deterioration due to shaking can be prevented.
すなわち本発明は、カルバ型カルシトニン類を有効成分
とし、ゼラチンを0.01〜20%W/V含有し、pH
5〜7であることを特徴とするカルバ型カルシトニン類
の水溶液組成物に関する。That is, the present invention uses carba-type calcitonin as an active ingredient, contains gelatin at 0.01 to 20% W/V, and has a pH of
The present invention relates to an aqueous solution composition of carba-type calcitonins, characterized in that the number of calcitonins is 5 to 7.
本発明において、カルバ型カルシトニン類とは、天然型
のカルシトニン類の1.7位のS−8結合をアミノスベ
リン酸にてC−C結合に変えたカルシトニン誘導体であ
り、例えば、カルバ型ウナギカルシトニン(WHO−船
名:エルカトニン)。In the present invention, carba-type calcitonins are calcitonin derivatives in which the S-8 bond at position 1.7 of natural calcitonins is changed to a C-C bond with aminosuberic acid, such as carba-type eel calcitonin. (WHO-Ship name: Elcatonin).
カルバ型ニワトリカルシトニン、カルバ型サケカルシト
ニン、カルバ型ブタカルシトニン、カルバ型ヒトカルシ
トニン等が挙げられる。Examples include carva-type chicken calcitonin, carva-type salmon calcitonin, carva-type porcine calcitonin, and carva-type human calcitonin.
ゼラチンは、分子量5,000〜50.000の加水分
解された純度の高い精製ゼラチンが好ましい。ゼラチン
の含有量は0.01〜20%W/Vであるが、好ましく
は0.1〜5%W/Vである。The gelatin is preferably hydrolyzed purified gelatin with a molecular weight of 5,000 to 50,000. The content of gelatin is 0.01 to 20% W/V, preferably 0.1 to 5% W/V.
また、pHを5〜7に調整するには、pH緩衝剤をその
水溶液組成物のpHを一定に保ち得る最低量で用いれば
よい。pH緩衝剤としては、医療上添加可能なpH緩衝
作用を有するものが用いられ、例えば、酢酸、コハク酸
、マレイン酸、乳酸。Further, in order to adjust the pH to 5 to 7, the pH buffer may be used in the minimum amount that can keep the pH of the aqueous composition constant. As the pH buffering agent, one having a pH buffering effect that can be added medically is used, such as acetic acid, succinic acid, maleic acid, and lactic acid.
クエン酸、酒石酸等の弱酸とそれらの酸のナトリウム塩
またはカリウム塩との組合せにより製したものがある。Some products are made by combining weak acids such as citric acid and tartaric acid with sodium or potassium salts of these acids.
その使用量は、例えば、クエン酸ナトリウム、酢酸ナト
リウムまたはマレイン酸ナトリウムを用いれば、0.0
5〜50m Mが好ましい。The amount used is, for example, 0.0 when using sodium citrate, sodium acetate or sodium maleate.
5-50mM is preferred.
活性成分であるカルバ型カルシトニンの含有量は、水溶
液組成物中の濃度として通常0.1〜100μg /
mlが好ましい。The content of carba-type calcitonin, which is an active ingredient, is usually 0.1 to 100 μg/concentration in an aqueous solution composition.
ml is preferred.
さらに必要に応じて、薬学上許容される安定化剤、増粘
剤、溶解補助剤、界面活性剤、保存剤。Furthermore, if necessary, pharmaceutically acceptable stabilizers, thickeners, solubilizing agents, surfactants, and preservatives.
増量剤1等張化剤等を加えることができる。Bulking agents, tonicity agents, etc. can be added.
増粘剤としては水溶性粘性物質であればよく、例えば、
メチルセルロース、ヒドロキシプロピルセルロース、カ
ルボキシビニルポリマー、プロピレングリコール、グリ
セリン、ポリエチレングリコール、ポリグリセリン、ポ
リビニルアルコール。The thickener may be any water-soluble viscous substance, for example,
Methylcellulose, hydroxypropylcellulose, carboxyvinyl polymer, propylene glycol, glycerin, polyethylene glycol, polyglycerin, polyvinyl alcohol.
ポリビニルピロリドン、ポリ乳酸、ヒドロキシプロピル
メチルセルロース、ヒドロキシプロピルスターチ、プル
ラン、カルボキシメチルセルロース。Polyvinylpyrrolidone, polylactic acid, hydroxypropylmethylcellulose, hydroxypropylstarch, pullulan, carboxymethylcellulose.
ヒアルロン酸、キトサン、コンドロイチン硫酸。Hyaluronic acid, chitosan, chondroitin sulfate.
ポリアミノ酸等が挙げられる。Examples include polyamino acids.
保存剤としては、パラオキシ安息香酸メチル。Methyl paraoxybenzoate is used as a preservative.
パラオキシ安息香酸プロピル、パラオキシ安息香酸エチ
ル等のパラベン類、2−フェニルエタノ−ル、エチルア
ルコール、クロロブタノール等のアルコール類、塩化ベ
ンザルコニウム、塩化ベンゼトニウム、塩化セチルピリ
ジニウム等のカチオン界面活性剤を使用してもよい。Parabens such as propyl paraoxybenzoate and ethyl paraoxybenzoate, alcohols such as 2-phenylethanol, ethyl alcohol, and chlorobutanol, and cationic surfactants such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium chloride are used. You may.
界面活性剤としては、非イオン活性剤が好ましく、例え
ば次のようなものが使用できる。As the surfactant, nonionic surfactants are preferred, and for example, the following can be used.
ポリオキシエチレンソルビタン脂肪酸エステル類として
は、例えば花王アトラス社製EMASOL +130(
POEソルビタンモノラウレート:HLB163) 、
EMASOL 3130 (POEソルビタンモノ
ステアレート:HLBI4.9) 、 TWEEN 2
0 (POE(20)ソルビタンモノラウレート: H
LB16.7) 、 TWEEN 40 (p o E
(20)ソルビタンモノパルミテート:HL B15
.6) 、 TWEEN 60 (POE (20)ソ
ルビタンモノステアレート: HL B 14.9)
、 TWEEN 80 (POE (20)ソルビタン
モノオレイト:HLBI5.0)。Examples of polyoxyethylene sorbitan fatty acid esters include EMASOL +130 (manufactured by Kao Atlas Co., Ltd.).
POE sorbitan monolaurate: HLB163),
EMASOL 3130 (POE sorbitan monostearate: HLBI4.9), TWEEN 2
0 (POE(20) sorbitan monolaurate: H
LB16.7), TWEEN 40 (p o E
(20) Sorbitan monopalmitate: HL B15
.. 6), TWEEN 60 (POE (20) Sorbitan Monostearate: HL B 14.9)
, TWEEN 80 (POE (20) sorbitan monooleate: HLBI5.0).
日光ケミカルズ社製NIKKOL TL−1010、T
P−10。NIKKOL TL-1010, T manufactured by Nikko Chemicals
P-10.
TS−10、TO−10M、 日本油脂社製ノニオン
0T−221゜ノニオン5T−221,ノニオンPT−
221,ノニオンLT−221などが挙げられる。TS-10, TO-10M, Nonion 0T-221゜Nonion 5T-221, Nonion PT- manufactured by NOF Corporation
221, Nonion LT-221, and the like.
ポリオキシエチレン硬化ヒマシ油としては、例えば日光
ケミカルズ社製NIKKOL lIC0−40(P O
E(40)硬化ヒマシ油: HLB 12.5 ) 、
NIKKOL lIc0−50 (P OE (5
01硬化ヒマシ油:HLBI3.5)NIKKOL H
CO−60(P OE (60)硬化ヒマシ油: HL
BI4.0)、 日本油脂社製ユニオックスlIc−
40。Examples of polyoxyethylene hydrogenated castor oil include NIKKOL IC0-40 (PO
E(40) hydrogenated castor oil: HLB 12.5),
NIKKOL lIc0-50 (P OE (5
01 hydrogenated castor oil: HLBI3.5) NIKKOL H
CO-60 (P OE (60) hydrogenated castor oil: HL
BI4.0), Uniox lIc- manufactured by Nippon Oil & Fats Co., Ltd.
40.
ユニオックスlIc−50、ユニオックス+1 C−6
0などか挙げられる。Uniox lIc-50, Uniox +1 C-6
Examples include 0.
ポリオキシエチレンソルビット脂肪酸エステル類として
は、例えば日光ケミカルズ社製NIKKOLGO−43
0(P OE (30)ソルビットテトラオレエートH
LB 11.5)、 NIKKOLGO−440(
POE(40)ソルビットテトラオレエート:HLB1
2.5)、 NIKKOL Go−460(P OE
(60)ソルビットテトラオレエート: HLB 1
4.OL NIKKOL GL−1(POE(61ソ
ルビットラウレート・HLB 15.5)、花王アトラ
ス社製^TLOX 1045^(POEソルビトールオ
レイトーラウレート:HLB 13.2+、 AT
LOX +196(POEソルビトールオレイト: H
L B I+、 4)。Examples of polyoxyethylene sorbitol fatty acid esters include NIKKOLGO-43 manufactured by Nikko Chemicals Co., Ltd.
0(P OE (30) Sorbittetraoleate H
LB 11.5), NIKKOLGO-440 (
POE (40) Sorbittetraoleate: HLB1
2.5), NIKKOL Go-460 (POE
(60) Sorbittetraoleate: HLB 1
4. OL NIKKOL GL-1 (POE (61 sorbitol laurate/HLB 15.5), manufactured by Kao Atlas TLOX 1045^ (POE sorbitol oleitol laurate: HLB 13.2+, AT
LOX +196 (POE sorbitol oleate: H
LBI+, 4).
G−1045(P OEソルビトールラウレート: H
LBll、5)、 G−1441(POEソルビトール
ラノリン誘導体:HLBI4.0)などが挙げられる。G-1045 (POE sorbitol laurate: H
LBll, 5), G-1441 (POE sorbitol lanolin derivative: HLBI4.0), and the like.
ポリオキシエチレングリセリン脂肪酸エステル類とシテ
ハ、例えばNIKKOLTMGS−15(POE(+5
)グリセリルモノステアレート:HLB 13.51
゜NIKKOL TMGS−5(P OE (5)グリ
セリルモノステアレート:HLB9.5)などが挙げら
れる。Polyoxyethylene glycerin fatty acid esters and shiteha, such as NIKKOLTMGS-15 (POE (+5
) Glyceryl monostearate: HLB 13.51
Examples include NIKKOL TMGS-5 (POE (5) glyceryl monostearate: HLB 9.5).
ポリエチレングリコール脂肪酸エステル類としては、例
えば日光ケミカルズ社製NIKKOL MYL−IIO
(POE(10)モノラウレート:HLB12.5)。Examples of polyethylene glycol fatty acid esters include NIKKOL MYL-IIO manufactured by Nikko Chemicals Co., Ltd.
(POE(10) monolaurate: HLB12.5).
NIKKOL MYL−10(P OE (10)モノ
ステアレート:HLBll、0) 、 NIKにOL
MYL−40(P OE (40) −T−/ステア
レート:HLB17.5)などが挙げられる。NIKKOL MYL-10 (P OE (10) Monostearate: HLBll, 0), OL to NIK
Examples include MYL-40 (P OE (40) -T-/stearate: HLB17.5).
ポリオキシエチレンアルキルフェニルエーテル類として
は、例えば日光ケミカルズ社製旧KKOLNP−10(
POE(In1ノニルフェニルエーテル:HLBI6.
5) 、 NIKKOL 0P−10(POE(10
)オクチルフェニルエーテル:HLBIl、5)、花王
アトラス社製EMULGEN 810 (P OEオク
チルフェニルエーテル: HLB13.1) 、 E
MULGEN 911 (POEノニルフェニルエーテ
ル: HL B 13.71 、 EMULGEN9
30(POEノニルフェニルエーテル:HLBI51)
、 EMULGEN 950 (POE/ニル7
、 = ルz −チル:HLB18.2)などが挙げら
れる。As polyoxyethylene alkyl phenyl ethers, for example, former KKOLNP-10 manufactured by Nikko Chemicals Co., Ltd.
POE (In1 nonylphenyl ether: HLBI6.
5), NIKKOL 0P-10 (POE (10
) Octylphenyl ether: HLBIl, 5), EMULGEN 810 manufactured by Kao Atlas (POE octylphenyl ether: HLB13.1), E
MULGEN 911 (POE nonylphenyl ether: HL B 13.71, EMULGEN9
30 (POE nonylphenyl ether: HLBI51)
, EMULGEN 950 (POE/Nil 7
, =ruz-chill:HLB18.2), and the like.
これらの非イオン界面活性剤のHLB価は8〜18、好
ましくは10〜17である。The HLB value of these nonionic surfactants is 8-18, preferably 10-17.
等張化剤としては薬学上許容されている一般的なもので
あればよく、例えばNaC1,KCI等の無機塩類、単
糖類、三糖類等が使用できる。The tonicity agent may be any general pharmaceutically acceptable agent, such as inorganic salts such as NaCl and KCI, monosaccharides, trisaccharides, and the like.
このようにして得られた水溶液組成物は、例えばアンプ
ル、バイアルビン等の医薬用ガラス容器またはプラスチ
ック容器に注入して常法により水溶液注射剤とすること
ができ、また、水溶液の経鼻投与剤の主剤とすることが
できる。しかしながら、例えばホウケイ酸ガラスやソー
ダ石灰ガラスにて成形された容器内に水や酸が作用する
と、その表面からのアルカリ成分の溶出等の外的要因に
より、水溶液組成物のpHの変動を生ずる場合がある。The aqueous solution composition thus obtained can be injected into a pharmaceutical glass container or plastic container such as an ampoule or a vial to obtain an aqueous solution injection by a conventional method, or an aqueous solution for nasal administration. It can be used as the main ingredient. However, when water or acid acts on a container made of borosilicate glass or soda lime glass, for example, the pH of the aqueous solution composition may change due to external factors such as elution of alkaline components from the surface. There is.
このような場合には、ガラス容器表面のアルカリ成分を
選択的に洗浄、除去する方法として、例えば250〜8
00℃程度の高温状態のガラス表面に亜硫酸ガスや硫酸
アンモニウム等の水溶性イオウ酸化物を接触させて、表
面のアルカリ成分を微細な硫酸塩結晶となし、その後洗
浄する脱アルカリ処理等の特殊加工した容器或いは外的
にpH変動を引き起こさない特殊容器を用いることが望
ましい。In such a case, as a method of selectively cleaning and removing alkaline components on the surface of the glass container, for example, 250 to 8
Special processing such as dealkalization treatment, in which water-soluble sulfur oxides such as sulfur dioxide gas and ammonium sulfate are brought into contact with the glass surface at a high temperature of around 00°C, converts the alkaline components on the surface into fine sulfate crystals, which are then washed. It is desirable to use a container or a special container that does not cause external pH fluctuations.
(実施例)
以下に実施例及び実験例を挙げて本発明を更に詳しく説
明するが、本発明はこれらに限定されるものではない。(Example) The present invention will be explained in more detail with reference to Examples and Experimental Examples below, but the present invention is not limited thereto.
実施例1゜
5mMのクエン酸ナトリウム液と5mMクエン酸液を混
合し、pH6,0のpH緩衝液200m1を調製し、こ
れ・に更に塩化ナトリウムを0.9%W/■、加水分解
ゼラチン(分子置駒10.000)を1%W/Vとなる
よう加えて溶解した。この溶液100m1にカルバ型ウ
ナギカルシトニン1■を溶解し、カルバ型ウナギカルシ
トニン水溶液組成物を調製した。Example 1 5mM sodium citrate solution and 5mM citric acid solution were mixed to prepare 200ml of pH buffer solution with pH 6.0. To this, sodium chloride was further added at 0.9% W/■, and hydrolyzed gelatin ( A molecular weight of 10,000) was added and dissolved at 1% W/V. One part of carva-type eel calcitonin was dissolved in 100 ml of this solution to prepare a carba-type eel calcitonin aqueous solution composition.
次にこの水溶液組成物をアンプルに1mlずつ充填し、
カルバ型ウナギカルシトニンのアンプル剤を製した。な
お以上の操作は全て無菌的に行った。Next, fill each ampoule with 1 ml of this aqueous solution composition,
An ampoule of carba-type eel calcitonin was prepared. All of the above operations were performed aseptically.
実施例′2゜
実施例1と同様の0.9%塩化ナトリウム、1%ゼラチ
ンを含むpH6,0のクエン酸緩衝液100m1に、カ
ルバ型ニワトリカルシトニン1■を溶解し、カルバ型ニ
ワトリカルシトニン水溶液組成物を調製した。Example '2゜ Carva-type chicken calcitonin (1) was dissolved in 100 ml of a citric acid buffer with a pH of 6.0 containing 0.9% sodium chloride and 1% gelatin as in Example 1 to prepare a carva-type chicken calcitonin aqueous solution composition. I prepared something.
次にこの水溶液組成物を実施例1と同様にアンプルに充
填し、カルバ型ニワトリカルシトニンのアンプル剤を製
した。Next, this aqueous solution composition was filled into an ampoule in the same manner as in Example 1 to prepare an ampoule of carba-type chicken calcitonin.
対照例1゜
実施例1の水溶液においてゼラチンのみを含まない、0
.9%塩化ナトリウム含有pH6,0のクエン酸緩衝液
100 mlに、カルバ型ウナギカルシトニン1■を溶
解し、この水溶液組成物を実施例1と同様アンプルに充
填し、カルバ型ウナギカルシトニンのアンプル剤を製し
た。Control example 1゜The aqueous solution of Example 1 does not contain only gelatin, 0
.. In 100 ml of a citrate buffer solution containing 9% sodium chloride and pH 6.0, 1 part of carva-type eel calcitonin was dissolved, and this aqueous solution composition was filled into ampoules in the same manner as in Example 1. Manufactured.
対照例2゜
実施例1の水溶液においてゼラチンのみを含まない、0
.9%塩化ナトリウム含有pH6,0のクエン酸緩衝液
100 mlにカルバ型ニワトリカルシトニン1mgを
溶解し、この水溶液組成物を実施例1と同様アンプルに
充填し、カルバ型ニワトリカルシトニンのアンプル剤を
製した。Control Example 2゜The aqueous solution of Example 1 does not contain only gelatin, 0
.. 1 mg of carva-type chicken calcitonin was dissolved in 100 ml of a citrate buffer solution containing 9% sodium chloride and pH 6.0, and this aqueous solution composition was filled into ampoules in the same manner as in Example 1 to prepare an ampoule of carva-type chicken calcitonin. .
実験1゜
実施例1.2及び対照例1,2のアンプル剤を40°の
恒温器に3ケ月間保存し、各経時にカルバ型ウナギカル
シトニン及びカルバ型ニワトリカルシトニンの含量残存
率を高速液体クロマトグラフィーにて測定した。Experiment 1゜The ampoules of Example 1.2 and Control Examples 1 and 2 were stored in a constant temperature chamber at 40° for 3 months, and the remaining content of carva-type eel calcitonin and carba-type chicken calcitonin was measured by high-performance liquid chromatography at each time. It was measured using a graph.
高速液体クロマトグラフィー測定条件
カラL :ODSカラム 4.6X 100m検出:U
V22a鵬
移動相: CHi CN−11,1%TFA (約1:
2)結果を以下の第1表に示す。High performance liquid chromatography measurement conditions Color L: ODS column 4.6X 100m detection: U
V22a Peng mobile phase: CHi CN-11, 1% TFA (approximately 1:
2) The results are shown in Table 1 below.
〈第1表〉
第1表に示す通り、本発明の組成物である実施例1.2
のアンプル剤は熱に対する安定性が向上していた。<Table 1> As shown in Table 1, Example 1.2, which is a composition of the present invention
The ampules had improved stability against heat.
実験2゜
実施例1,2、及び対照例1.2のアンプル剤を恒温振
盪機中にて14日間振盪し、カルバ型ウナギカルシトニ
ン及びカルバ型ニワトリカルシトニンの含量残存率を実
験1と同じ条件にて各経時に測定した。Experiment 2゜The ampoules of Examples 1 and 2 and Control Example 1.2 were shaken in a thermostatic shaker for 14 days, and the remaining content of carva-type eel calcitonin and carva-type chicken calcitonin was maintained under the same conditions as in Experiment 1. Measurements were made at each time point.
振盪条件 振 幅:10cm 振盪回数、120回/分 温 度:25℃ 結果を第2表に示す。Shaking conditions Width: 10cm Number of shaking: 120 times/min Temperature: 25℃ The results are shown in Table 2.
く第2表〉
第2表に示す通り、本発明の組成物である実施例1.2
のアンプル剤は、振盪に対して極めて安定であった。Table 2 As shown in Table 2, Example 1.2, which is a composition of the present invention
The ampoules were extremely stable to shaking.
[発明の効果]
本発明のカルバ型カルシトニン類水溶液組成物は、振盪
に対して安定であり、また熱に対しても安定である。従
って、本発明の組成物は、輸送中の振盪や高温という条
件にさらされても従来のように活性を低下させることが
ない。[Effects of the Invention] The aqueous solution composition of carba-type calcitonins of the present invention is stable against shaking and also stable against heat. Therefore, even if the composition of the present invention is exposed to shaking or high temperature conditions during transportation, its activity does not decrease as in the case of conventional compositions.
Claims (6)
ンを0.01〜20%W/V含有し、pH5〜7である
ことを特徴とするカルバ型カルシトニン類の水溶液組成
物。(1) An aqueous solution composition of carba-type calcitonins, which contains carba-type calcitonins as an active ingredient, contains 0.01 to 20% W/V of gelatin, and has a pH of 5 to 7.
シウム低下作用を有するポリペプチド系カルシトニン類
の1〜7位のS−S結合をアミノスベリン酸にてC−C
結合に改変した少なくとも血清カルシウム低下作用を有
するポリペプチド類である請求項1記載の水溶液組成物
。(2) Carba-type calcitonins connect the S-S bonds at positions 1 to 7 of polypeptide calcitonins, which have at least a serum calcium-lowering effect, with aminosuberic acid to C-C
The aqueous solution composition according to claim 1, which is a polypeptide having at least a serum calcium-lowering effect with modified binding.
シトニン、カルバ型ニワトリカルシトニン、カルバ型サ
ケカルシトニン、カルバ型ヒトカルシトニンまたはカル
バ型ブタカルシトニンである請求項1記載の水溶液組成
物。(3) The aqueous solution composition according to claim 1, wherein the carva-type calcitonin is carva-type eel calcitonin, carva-type chicken calcitonin, carva-type salmon calcitonin, carba-type human calcitonin, or carva-type porcine calcitonin.
る濃度として0.1〜100μg/mlである請求項1
記載の水溶液組成物。(4) The concentration of the carba-type calcitonin in the aqueous solution composition is 0.1 to 100 μg/ml.
The aqueous composition described.
加水分解された精製ゼラチンである請求項1記載の水溶
液組成物。(5) The aqueous solution composition according to claim 1, wherein the gelatin is purified hydrolyzed gelatin having a molecular weight of 5,000 to 50,000.
剤を含有してなる請求項1記載の水溶液組成物。(6) The aqueous solution composition according to claim 1, which contains a buffering agent of 0.05 to 50 mM.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2243807A JPH0674209B2 (en) | 1990-09-17 | 1990-09-17 | Method for stabilizing carba type calcitonin aqueous solution injection |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2243807A JPH0674209B2 (en) | 1990-09-17 | 1990-09-17 | Method for stabilizing carba type calcitonin aqueous solution injection |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH04128241A true JPH04128241A (en) | 1992-04-28 |
JPH0674209B2 JPH0674209B2 (en) | 1994-09-21 |
Family
ID=17109231
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2243807A Expired - Lifetime JPH0674209B2 (en) | 1990-09-17 | 1990-09-17 | Method for stabilizing carba type calcitonin aqueous solution injection |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH0674209B2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09502424A (en) * | 1993-06-29 | 1997-03-11 | フエリング ビー ヴイ | Stabilized pharmaceutical peptide composition |
JP2007505045A (en) * | 2003-09-08 | 2007-03-08 | ゼンゲン・インコーポレイテッド | Compositions and methods for treating urogenital symptoms |
-
1990
- 1990-09-17 JP JP2243807A patent/JPH0674209B2/en not_active Expired - Lifetime
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09502424A (en) * | 1993-06-29 | 1997-03-11 | フエリング ビー ヴイ | Stabilized pharmaceutical peptide composition |
JP2007505045A (en) * | 2003-09-08 | 2007-03-08 | ゼンゲン・インコーポレイテッド | Compositions and methods for treating urogenital symptoms |
Also Published As
Publication number | Publication date |
---|---|
JPH0674209B2 (en) | 1994-09-21 |
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